Wounds, also referred to as skin lesions, show various symptoms, e.g., pain, bleeding, scar formation, dysfunction and so on. Wound healing involves processes such as inflammatory response, granulation tissue formation, re-epithelialization and angiogenesis etc. The processes include the actions of various growth factors, cytokines, neuronal hormones, etc. secreted from fibroblasts, adipocytes, blood-derived cells, and sensory neurons, leading to epidermal cell proliferation and extracellular matrix formation.
For regenerating connective tissues or maintaining the elasticity and strength of intact connective tissues without destruction thereof, it is important to form and maintain the extracellular matrix (ECM) proteins, such as type I, III collagens, elastin, fibronectin, etc., present in the skin. Natural aging or chronic exposure to ultraviolet radiation results in loss of the ECM proteins and reduced elasticity and strength of skin tissues, which are associated strongly with the characteristics of skin aging, such as wrinkle formation. Matrix metalloproteinases (MMPs) act as a key enzyme in degrading the dermal ECM. Over-expression of MMPs in keratinocytes and dermal fibroblasts under stress conditions, such as ultraviolet irradiation, contributes to degradation of the ECM proteins, thereby forming wrinkles on the skin.
An inflammatory response is known as a protective response of living organism for rehabilitating the structures and functions of tissues damaged by infection, trauma, etc. Mobilization of leukocytes to a focus of inflammation is critical for the rapid resolution of infections and restoration of tissue damages resulting from a variety of injuries. However, a misdirected or prolonged inflammatory response causes damage to the body's tissues or diseases. For example, inflammatory diseases are caused by bacterial or viral infection, e.g., cerebrospinal meningitis, enteritis, dermatitis, uveitis, encephalitis, or adult respiratory distress syndrome, or non-infectious factors, e.g., trauma, autoimmune diseases, or organ transplantation rejection. Inflammatory diseases are classified into acute and chronic inflammatory diseases according to symptoms or pathological features. Acute inflammation such as allergy or bacterial/viral infection is manifested as local signs such as a change in bloodstream, blood vessel size, and vascular permeability, and the recruitment of leukocytes. In contrast, a main pathological feature of chronic inflammation such as rheumatoid arthritis, artherosclerosis, chronic kidney infection, or hepatocirrhosis is a continuous emigration of macrophages, lymphocytes, or plasma cells into foci of inflammation due to recurrence of inflammatory factors, thereby causing a long-lasting inflammatory response.
In order to induce an inflammatory response, the emigration of leukocytes into inflammation foci is an essential event. Many cell adhesion molecules are implicated in the emigration of leukocytes. That is, the emigration of leukocytes includes a rolling stage in which leukocytes are mobilized to the blood vessels of inflamed sites by chemokine secreted from the inflamed sites and then rolled on surfaces of vascular endothelial cells while reducing the velocity of cell movement; an adhesion stage in which the leukocytes stops rolling and are firmly adhered to the vascular endothelial cells; and a transmigration stage wherein the leukocytes migrate through capillary vessels and basement membranes. The final stage, i.e., the transmigration stage is also called “diapedesis”.
Cancer cells induced by carcinogens proliferate rapidly relative to normal cells, thereby forming tumor masses, invading surrounding tissues, and interfering with normal body functions. Cancer cells bring nutrients and oxygen by inducing angiogenesis, and metastasis thereof is also caused by angiogenesis. Although cancer cells grow infinitely at specific sites, they can also leave the sites from which they originated, migrate to and grow in new sites, whose process is called “metastasis”. Metastasis involve several key steps: conversion of cancer cells to migratory mesenchymal cells, dissociation of the mesenchymal cells from the original tumor sites, invasion into and spread through surrounding connective tissues and capillary vessels, migration through blood vessels, escape from the blood vessels, migration through connective tissues, and proliferation in secondary sites.
Meanwhile, adiponectin is one of the adipokines, protein hormones secreted specifically in adipocytes. Adiponectin promotes the function of insulin and induces insulin resistance, thereby playing an important role in controlling cardiovascular diseases, such as hyperglycemia, hyperinsulinemia, obesity, and arteriosclerosis. And also, adiponectin has the functions for suppressing metastasis of cancer cells and inflammatory response. Adiponectin also performs the functions of wound healing, fibrosis inhibition, amelioration of skin wrinkle, and moisturization, by facilitating the expressions of filaggrin, hyaluronic acid, and extracellular matrix as well as the proliferation of keratinocytes in the skin.